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    Map of Kenya showing the location of West Pokot district and the distribution of suspected meningococcal meningitis cases among 37 of 39 cases enrolled in the case-control, showing the proximity of cases to Uganda where the outbreak began, 2005–2006.

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    Cases of suspected meningococcal meningitis by week, West Pokot, Kenya, November 2005 to April 2006.

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Epidemiology and Risk Factors for Serogroup X Meningococcal Meningitis during an Outbreak in Western Kenya, 2005–2006

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  • 1 Field Epidemiology and Laboratory Training Program – Kenya, Centers for Disease Control and Prevention and Kenya Ministry of Public Health and Sanitation, Nairobi, Kenya; US Naval Medical Research Program 3, Cairo, Egypt; Division of Disease Surveillance and Response, Ministry of Health, Nairobi, Kenya; African Medical Research Foundation, Nairobi, Kenya; Meningitis Branch, Centers for Disease Control and Prevention, Atlanta, Georgia; International Emerging Infections Program, Kenya, Centers for Disease Control and Prevention, Nairobi, Kenya

The epidemiology of serogroup X meningococcal meningitis in Africa is unknown. During a serogroup X meningococcus outbreak in Kenya, case finding involved record review at health facilities and interviews with health workers and community leaders in West Pokot district. An age- and location-matched case-control study for risk factors was done. From December 2005 to April 2006, 82 suspect cases of meningitis were reported; the epidemic threshold was surpassed within two administrative divisions. Most (58%) cases were 5–24 years old; the case-fatality ratio was 21%. Serogroup X meningococcus was the most common serogroup – 5 (63%) of eight isolates serogrouped. Living in the same compound as another case, preceding upper respiratory tract infection and cooking outside the house were significant risk factors for disease. Serogroup X meningococcus caused an outbreak with similar epidemiology and risk factors as other serogroups. Serogroup-specific laboratory-based surveillance for meningococcus in Africa to detect serogroup X disease should be enhanced.

INTRODUCTION

Meningococcal meningitis continues to be a devastating disease in Africa, especially in areas where access to health services is poor. 1,2 The greatest burden of meningococcal meningitis occurs in sub-Saharan Africa, mostly concentrated in the so-called meningitis belt running along the southern border of the Sahara desert.13 In the meningitis belt, high levels of endemic disease are punctuated by large epidemics in 8–12-year cycles during the dry season, affecting thousands of people. 1,3,4 Large, seasonal African meningitis epidemics are caused mostly by Neisseria meningitidis serogroup A. Other serogroups of meningococcus cause endemic disease with occasional, localized outbreaks.1 Serogroup C meningococcus was responsible for a large outbreak in Upper Volta (now Burkina Faso) in 1979. 1,3,5 In 2002, a large epidemic of serogroup W-135 occurred in Burkina Faso in West Africa. 6,7 Before 2006, serogroup X meningococcus had been isolated as a cause of meningitis in Niger and Ghana in relatively low numbers.810 In 2006, serogroup X was the most commonly isolated serogroup of meningococcus isolated from seasonal meningitis cases in Niger, surpassing serogroup A. 11

In December 2005, cases of meningococcal meningitis occurred in the Nakapiripirit region of Uganda, which borders the West Pokot district of Kenya. 12 The area is a few hundred kilometers south of the meningitis belt. By late December, cases of meningitis occurred among Kenyans living in a rural, remote area of West Pokot, with limited access to health facilities. The first outbreak-associated isolates in Uganda were serogroup A meningococcus. 12,13 Initially, because of the remoteness of the area where the first cases associated with the outbreak in Kenya were observed, few patients had lumbar punctures done, and it was assumed that serogroup A was responsible for causing disease. However, several weeks into the Kenyan outbreak, laboratory results showed that serogroup X meningococcus was the predominant serogroup involved. 14 Serogroup X meningococcus was also later identified in Uganda. 13,14 Because of the paucity of epidemiologic data on serogroup X meningococcal meningitis, we undertook a study to better define the clinical characteristics, demographic features, and risk factors for serogroup X meningococcal meningitis in the outbreak in Kenya.

MATERIALS AND METHODS

Case finding.

A suspected case of meningococcal meningitis was defined as any resident of West Pokot district with history of acute onset of fever and any one of the following signs: neck stiffness, altered consciousness, or petechial rash, or a child < 18 months of age with history of acute onset of fever and a bulging fontanelle. Only cases presenting at a health facility or who died in the community with compatible symptoms were included. A confirmed case was a suspected case in which N. meningitidis was isolated by bacterial culture or detected by polymerase chain reaction (PCR) from cerebrospinal fluid specimens. Case-finding was done by review of medical records and registers at all inpatient and outpatient health facilities in West Pokot District and interviews with health workers and community leaders. In late January, the District MOH distributed information to all the facilities in affected divisions on proper case management of meningitis cases and instituted daily reporting of new suspect cases. Ceftriaxone was distributed to all facilities in these divisions.

The epidemic threshold for this outbreak was defined as per World Health Organization (WHO) guidelines. Ten cases per 100,000 inhabitants in a week where the population is ≥ 30,000 people or five cases per 100,000 inhabitants in a week where the population is < 30,000 people was considered an epidemic. 15

Laboratory analysis.

The laboratory workup of suspect cases has been described previously. 14 In brief, lumbar punctures were done on suspected cases of meningitis at Kapenguria District Hospital and Amudat Hospital, across the border in Uganda. Cerebral spinal fluid (CSF) was sent on trans-isolate media to Nairobi for culture and identification at the African Medical Research Foundation (AMREF) laboratories. Two isolates of N. meningitidis, as well as seven CSF specimens, were sent to the Naval Medical Unit-3 (NAMRU-3) in Cairo for serogroup-specific testing using meningococcal serogroup-specific antisera (Becton Dickinson, Sparks, MD) and real-time PCR as previously described. 16,17 Multi-locus sequence typing (MLST) analysis was conducted on DNA extracted from isolates and CSF that showed robust amplified bands by N. meningitidis–specific MLST primers. 18 Antimicrobial susceptibility testing was performed by the E-test method according to the manufacturer’s instructions (AB Biodisk, Solna, Sweden).

Case-control study.

We conducted a matched case-control study of risk factors for meningitis in the two divisions of West Pokot district with the highest attack rates: Kacheliba and Alale (Figure 1). Cases included in the study were defined as residents of these divisions who met the suspect case definition for meningococcal meningitis with onset after December 15, 2005. Among cases that died, a knowledgeable proxy was sought to answer the questions. Three age-matched controls were enrolled from the neighborhood of each case. The controls were matched to the cases by age according to the following categories: for cases < 2 years of age, within 6 months of the case’s age; for cases 2–5 years of age, within 1 year of the case’s age; for cases 6–15 years of age, within 2 years of the case’s age; and for cases > 15 years of age, within 5 years of the case’s age. To be eligible, controls had to be residents of the area since September 15, 2005 and to not have had symptoms of meningitis since December 15, 2005. From the household of each enrolled case, the interviewer spun a bottle, and the first control was selected from the first household in the direction the bottle pointed. Where there was no matching control in the identified household, the interviewer proceeded to the next household in the same direction until a matching control was identified. From the household of the first enrolled control, the bottle was spun again, and the second control was selected in a similar manner. This was repeated until three controls were identified. A household was defined as a group of people who cooked and fed from the same pot, whereas a compound was defined as a cluster of households that is closely related, especially an extended family.

Based on a sample size calculation of an estimated prevalence of 30% of a risk factor among the cases and 10% among controls, with three controls enrolled for each case, a power of 80%, and an α of 0.05, the estimated sample size needed was 44 cases and 132 controls. Because of logistical reasons, however, we were able to enroll only 39 cases and 117 controls, and this provided 80% power to detect an odds ratio (OR) of 4.1 if the prevalence in cases was 31.3% and controls was 10%.

Data were collected by trained interviewers using a semi-structured questionnaire translated into the local language (Pokot). The questionnaire asked about characteristics of the household, recent travel, exposure to sick people, and having had a preceding upper respiratory tract infection (URTI), which was defined as having had cough, runny nose, sore throat, and/or sneezing in the 2 weeks before onset of meningitis symptoms. Surrogates for higher socioeconomic status were ownership of radios, televisions, bicycles, and motorbikes. We asked about the highest level of education obtained by each parent and evaluated whether this was associated with disease. Data were entered, cleaned, and analyzed in Epi-info 2002 (version 3.3.2.). Bivariate-matched analysis by stratification on the matched sets of participants was done, and all variables with P < 0.1 were included in multivariable analysis using conditional logistic regression model. Through a backward elimination process, significant risk factors with P < 0.05 were identified. Statistical interaction was assessed by inclusion of product terms in the model.

RESULTS

Descriptive epidemiology.

The first case of suspected meningococcal meningitis had an onset on December 4, 2005. By late April 2006, 82 suspect cases had been reported from West Pokot District (Figure 2). The outbreak peaked during the month of January 2006. Four of five divisions within the district reported cases. The WHO epidemic threshold was surpassed in two divisions: Kacheliba and Alale. 15 The weekly rate in Kacheliba division peaked at 36 per 100,000 (9 cases among 24,820 persons) and in Alale division at 11 per 100,000 (4 cases among 36,558 inhabitants). Eighty-two percent of reported cases occurred within these two divisions (44 cases in Kacheliba and 23 cases in Alale), most within 25 km of the border with Uganda (Figure 1). Only Kacheliba division had an overall attack rate > 100 per 100,000 inhabitants (133 per 100,000), with the overall attack rate for the entire district of West Pokot being 16 per 100,000 inhabitants over the entire period of the outbreak. Females accounted for 43 (52%) cases. The majority of cases (58%) were between 5 and 24 years of age (Table 1). The case-fatality ratio was 21% among the 76 cases with known outcomes; mortality varied by age (Table 1). Among the 39 cases in the case-control study for whom more detailed clinical information was available, the clinical presentation was similar to other types of meningococcal meningitis with fever and neck stiffness occurring in all patients, with approximately one fifth exhibiting signs of confusion or convulsions (Table 2). Rash was not observed. Patients with confirmed serogroup X meningococcus had a similar clinical presentation as cases without serogroup confirmation.

Laboratory.

Neisseria meningitidis serogroup X was isolated from two CSF specimens. 14 Both isolates were β-lactamase negative and susceptible to ampicillin (minimum inhibitory concentration [MIC] < 0.09 μg/mL) and ceftriaxone (MIC < 0.002 μg/mL). Besides the two culture-confirmed specimens, seven culture-negative CSF specimens were PCR positive for N. meningitidis.14 Of these seven CSF specimens, three were serogrouped as serogroup X, and one each was serogroup W-135, Y, and C. One specimen was non-groupable by real-time PCR. The MLST sequence type (ST) for all four specimens tested (two isolates and two culture-negative CSF identified as serogroup X by PCR with enough DNA for MLST) was ST-5403, which was an identical ST with the isolates from the concurrent Uganda outbreak. 14 The other five specimens had insufficient DNA for MLST analyses.

Case-control study.

A total of 156 people (39 cases and 117 controls) of the calculated sample of 176 persons were interviewed. This constituted 89% of the calculated sample. The cases came from 25 villages in the Kacheliba (72% of cases) and Alale divisions (28% of cases). Sixty-four percent of all recorded cases in Kacheliba and 48% of all recorded cases from Alale division were enrolled. The case-fatality ratio (CFR) among cases enrolled into the study (21%) was the same as the overall CFR for the outbreak. The age range of cases was between 3 and 60 years, with a median of 14 years; 13% of the cases were younger than 5 years of age and 59% were younger than 20 years of age. The median age of controls was 14 years, the same as cases because of matching. Forty-one percent of cases and 42% of controls were males (P > 0.05). The mean household size was seven people for cases and six people for controls, whereas the mean compound size was 18 people for cases and 15 people for controls (P > 0.05). The mean number of rooms per household was 1.2 for cases and 1.5 for controls, and the mean number of people sleeping in one room at the same time was 4.1 for cases and 3.5 among controls, with a mean of 3.0 people sharing a bed or sleeping mat among cases and 2.7 among controls (P > 0.05 for all comparisons).

In univariate analysis, illness was significantly associated with having another meningitis case in the compound, having had a preceding history of URTI, more than three people sharing a bed or a sleeping mat, cooking outside only, and crossing the border to Uganda. Having a household resident who smokes or spending over an hour with a smoker and attending large gatherings were borderline significant risk factors (Table 3). Factors that were not found to differ between cases and controls were having had other household members cross the border to Uganda, socioeconomic status of the household, sex, sniffing tobacco, drinking alcohol, level of education of the person or the parent, and occupation of the head of household.

In multivariable analysis, three risk factors were significant: having a case in the compound, preceding history of URTI, and cooking outside of the house only (Table 3). Of these, having another case in the compound was most strongly associated (OR = 36.2; 95% CI, 4.3–302).

DISCUSSION

We described the epidemiology of the first outbreak of serogroup X meningococcal meningitis outside of the African meningitis belt. Combining the cases from Kenya (both diagnosed and undiagnosed) with those in the bordering districts of Uganda, possibly several hundred cases occurred in December 2005 to April 2006. 1214 The exact number of cases of serogroup X disease remains unknown because the majority of cases did not have a lumbar puncture, many cases did not present to health facilities in these remote areas, and in both Kenya and Uganda, other serogroups besides X were isolated. 1214 Single cases of other serogroups likely represented detection of underlying, endemic meningococcal disease caused by multiple serotypes because of enhanced laboratory surveillance in the setting of the outbreak.

The increasing occurrence of serogroup X meningococcus in Africa highlights the need for serogroup identification when making decisions about vaccination during outbreaks. Although the serogroup had not yet been identified in Kenya by early March 2006, because cases of serogroup A had been identified across the border in Uganda where a vaccination campaign had already begun, when the epidemic threshold was surpassed in Kenya, a decision was made by the Kenyan MOH to vaccinate persons older than 2 years of age in the four affected divisions of West Pokot district with the trivalent polysaccharide vaccine (serogroups A, C, Y). 12,13,18 Vaccination was undertaken, with a total of 158,436 people recorded as being vaccinated in an area with a targeted population of ~148,000 people.

The clinical presentation of serogroup X meningitis in this outbreak did not differ from those of serogroup A meningitis outbreaks in Africa, assuming that most of the cases in this outbreak had meningococcal meningitis caused by serogroup X.1 However, we found a case-fatality rate of 21%, which was higher than in other African meningococcal outbreaks. This might have been because of the extreme remoteness of the area and the lack of clinical experience in handling meningococcal outbreaks, as well as underdetection of milder cases. Notably, serogroup X meningococcal meningitis in Niger (CFR, 12%; mean age, 7.9 years) and Ghana (CFR, 11%; mean age, 9.7 years) also showed similar age distribution, clinical features, and CFRs as serogroup A meningitis. 8,11

During 2006, Niger, within the meningitis belt, also experienced an increased incidence of serogroup X meningococcal meningitis, with > 500 cases occurring. 11 Despite the overlapping timing, the outbreaks in Niger and Kenya/Uganda were caused by different strains of the bacterium. 11,14 Niger has isolated more meningococcus serogroup X isolates than any other African country, with the first isolates from 1982. After a hiatus of 8 years, 22 cases were documented in 1990. 10,19 Between 1995 and 2000, cases of meningococcus serogroup X were detected annually, peaking with 83 cases in 1997. 10,19,20

Besides Niger, the other African location that has documented several cases of serogroup X meningococcal meningitis is northern Ghana, where from 1998 to 2000, nine cases occurred, coincident with a significant increase in serogroup X carriage. 8,9,21 This increase in carriage and disease of sero-group X meningococcus coincided with the disappearance of the dominant circulating strain of meningococcus serogroup A. 21 After a new serogroup A strain became dominant in late 2001, carriage and cases of serogroup X subsided. 21 The sero-group X strain that occurred in the Kenya/Uganda outbreak, ST-5403, is unrelated to the ST-181, ST-5789, and the ST-751 strains found in Niger and Ghana. 9,11,14 Outside of Niger and Kenya/Uganda, no other African countries documented an increase in serogroup X meningococcal disease during the 2006 meningitis season.

It has been postulated that other serogroups of meningococcus, such as serogroups W-135 and Y, are less virulent than serogroup A, as shown by a higher carriage to disease ratio. 22,23 A similar situation might occur with serogroup X. Consistent with the possibility of lower virulence is the pattern of serogroup X disease in Niger and Ghana, where it led to an increase in the rate of endemic disease and not large epidemics. 8,11 In addition, the ratio of cases to carriers was 40-fold higher for serogroup A than serogroup X in Ghana. 21 Despite this indirect evidence for lower virulence of serogroup X, the outbreak in Kenya and Uganda with several hundred cases showed that serogroup X can cause epidemics under the right conditions. What these conditions are remains a topic of speculation; however, they include introduction of a moderately virulent strain into a susceptible population.1 We did not perform a carriage study, so we could not make direct conclusions about the prevalence of the serogroup X carriage in the population or about its invasive potential from the colonizing state.

It is possible that serogroup X meningitis in Kenya/Uganda will follow a similar trajectory as serogroup W-135 disease in Burkina Faso. After introduction by Hajj pilgrims in 2000, a large outbreak resulted in Burkina Faso in 2002. 6,7 The sero-group W-135 outbreak in Burkina Faso, although sizable, remained limited in geography and time, never spreading to neighboring countries, and occurring in diminishing numbers in Burkina Faso itself in subsequent years. 24 As previously mentioned, a similar situation of a geographically limited epidemic followed by disappearance occurred with serogroup C meningitis in Burkina Faso in 1979. 1,5 Since the serogroup X outbreak of 2005/6, > 2 years have passed without emergence of serogroup X epidemics in any other African countries or in the same area of Kenya/Uganda.

The risk factors for meningitis during this outbreak of sero-group X meningococcus were similar to those found for other serogroups. Close contact with a case in the compound is a clear risk factor that has been shown before in Africa and in industrialized countries. 1,25 We also found that a preceding respiratory tract infection was a risk factor. This has also been shown before in Chad, where respiratory viruses and Mycoplasma species were associated with serogroup A meningitis during an outbreak. 26 In our study, we did not look at nasopharyngeal colonization to confirm that respiratory pathogens were more common in cases than controls, so it is possible that this finding could represent a misclassification bias related to the early symptoms of meningococcal disease in cases being mistakenly attributed to an upper respiratory tract infection.

The other risk factor identified in multivariable analysis, cooking outside only, is somewhat puzzling because direct exposure to cooking smoke, a known risk factor for meningococcal disease, would seem to be greater when cooking inside the small, unventilated dwelling that the Pokot usually live in. 25,27 We suspect that cooking outside represents households with fewer resources and might serve as a marker for lower socioeconomic status. Other markers of socioeconomic status, such as vehicle and television ownership, however, were not found to be associated with disease. Lower socioeconomic status was a risk factor for meningococcal disease in an urban African setting, although not in rural ones like this one where socioeconomic indicators tend to be more homogeneous. 25,28,29 Alternatively, it is possible that cooking outside led to an environmental factor, such as exposure to wind or dust, that might have placed these individuals at a higher risk of developing meningitis.

Of note, crossing the border into Uganda was a significant risk factor in univariate analysis. The same ethnic group lives on both sides of the border, and cross-border travel of the population is common to visit family, do business, and find pasture for cattle. As shown before, meningococcal meningitis does not respect borders and can spread along transportation routes, emphasizing that outbreaks should be approached on a regional rather than national scale. 1,6,7

Our study had several limitations. Because of the lack of availability of facilities to do lumbar puncture and culture CSF, most cases could not be confirmed. It is possible that some persons meeting the case definition for suspect menin-gococcal meningitis in our study did not have the disease. This would have led to overcounting of cases and misclassification in the case-control study. Moreover, for most clinically defined cases, it was unknown what the serogroup causing the illness was; therefore, the clinical and epidemiologic descriptions here might have not been specific to serogroup X. Serogroup X, however, accounted for the majority of microbiologically confirmed cases in Kenya. The number of confirmed cases of meningococcal disease could potentially have been increased by using newer diagnostic technologies, such as counterimmunoelectrophoresis and PCR, and specimens from other sources besides CSF, such as blood and skin biopsies. 30

The rising incidence of serogroup X meningitis in Africa is a potentially worrisome finding. Although it might not have the epidemic potential of serogroup A, the evidence here suggests that serogroup X can cause an epidemic. As with sero-groups W-135 and C, the epidemic potential of serogroup X becomes particularly important in light of the plans to introduce serogroup A conjugate vaccines in the meningitis belt in 2012. 31 A similar scenario might occur as did in some places with the introduction of the pneumococcal conjugate vaccine, in which serotypes not included in the vaccine have partially replaced those eliminated by the vaccine. 32 Because serogroup X meningococcal meningitis seems to have an indistinguishable clinical and epidemiologic picture and similar risk factors as serogroup A disease, it will be important to enhance laboratory-based surveillance to ensure serogroup identification among cases both before and after the introduction of the serogroup A conjugate vaccines. The experience with sero-group X disease in Uganda and Kenya highlights the critical need for accurate surveillance data for use in developing optimal vaccine formulations and effective prevention strategies.

Table 1

Age distribution, case-fatality ratio, and attack rates during an outbreak of serogroup X meningococcal meningitis, West Pokot, Kenya, 2005–2006

Table 1
Table 2

Signs and symptoms among 39 meningitis cases in the case-control study during outbreak of serogroup X meningococcal meningitis, West Pokot district, Kenya, 2005–2006

Table 2
Table 3

Univariate matched and multivariate analysis of risk factors for meningitis during an outbreak ofserogroup X meningococcal meningitis, West Pokot district, Kenya, 2005–2006

Table 3
Figure 1.
Figure 1.

Map of Kenya showing the location of West Pokot district and the distribution of suspected meningococcal meningitis cases among 37 of 39 cases enrolled in the case-control, showing the proximity of cases to Uganda where the outbreak began, 2005–2006.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 80, 4; 10.4269/ajtmh.2009.80.619

Figure 2.
Figure 2.

Cases of suspected meningococcal meningitis by week, West Pokot, Kenya, November 2005 to April 2006.

Citation: The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg 80, 4; 10.4269/ajtmh.2009.80.619

*

Address correspondence to Daniel R. Feikin, CDC, Unit 64112, APO, AE 09831. E-mail: dfeikin@ke.cdc.gov

Authors’ addresses: David M. Mutonga, Judith Muindi, and Christopher Tetteh, Field Epidemiology and Laboratory Training Program, CDC/KEMRI, Off Mbagathi Way, Nairobi, Kenya, Tel: +254-721203157, Fax: +254-572022981, E-mails: davidmutonga@yahoo.com, judithmuindi@yahoo.com, and TettehC@sa.cdc.gov. Guillermo Pimentiel, John D. Klena, and Myriam Morcos, U.S. Naval Research Program #3, Disease Surveillance Program, PSC 452 Box 116, FPO, AE 09835, Tel: +2-02-348-0333, Fax: +2-02-342-7121, E-mails: Guillermo.Pimentel@med.navy.mil, KlenaJ@namru3.med.navy.mil, and MorcosM@namru3.med.navy.mil. Charles Nzioka, Julius Mutiso, and Thomas Ogaro, Division of Disease Surveillance and Response, Kenya Ministry of Public Health and Sanitation, Afya House, Nairobi, Kenya, Tel: +254-733753541, E-mail: DOMU@africaonline.co.ke. Sadiki Matera, African Medical and Research Foundation, Langata Road, PO Box 27691, Nairobi, Kenya, Tel: +254-206993000, Fax: +254-20609518, E-mail: sadikim@amrefke.org. Nancy E. Messonnier, Division of Bacterial Diseases, Centers for Disease Control and Prevention, Mailstop C09, Atlanta, GA 30329-4018, Tel: 404-639-4734, E-mail: nar5@cdc.gov. Robert Breiman and Daniel Feikin, CDC/KEMRI, Unit 64112, APO, AE 09831, Tel: +254-202717529, Fax: +254-572022981, E-mails: rbreiman@ke.cdc.gov and dfeikin@ke.cdc.gov.

Acknowledgments: The authors thank the following people and institutions for their contribution in diverse ways: Ministry of Health Kenya, Disease Outbreak Management Unit officials, Jackson Njoroge, Rosalia Kalani; West Pokot District Ministry of Health Officials, Dr. Kimei, Chepkwony, Lokorkol Tarus, and Fred Machini; the community leaders, villagers, and the participants from West Pokot District.

Disclaimers: The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the US Department of the Navy. This information is distributed solely for the purpose of pre dissemination peer review under applicable information quality guidelines. It has not been formally disseminated by the Centers for Disease Control and Prevention. It does not represent and should not be construed to represent any agency determination or policy.

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